The insoluble 'high-molecular-weight' fraction (HMF) centrifugally separabl
e after digestion of soy protein isolate with a microbial protease of the e
xo-type, of which about a quarter is regarded as an indigestible 'resistant
protein,' was examined for its preventive effect against colonic tumorigen
esis in a model system with male F-344 rats, The rats were intraperitoneall
y injected with azoxymethane (15 mg/kg BW) once a week for 3 wk and were fe
d a 20.6% HMF diet (+0.4% DL-Met) or 14.7% casein diet (+0.3% DL-Met) suppl
emented with 0.2% sodium deoxycholate (DCA) or without supplementation. Twe
lve wk later, 5 rats of each group were inspected for formation of tumors b
ut no tumors were visible to the naked eye. The DCA-fed casein group was co
nspicuous for a low count of aberrant crypt foci, At 39 wk, 6 rats of the D
CA-fed casein group (n = 10) and 3 rats of the DCA-fed HMF group (n = 9) ha
d a total of 18 tumors with a major axis of 4.0+/-0.4 mm and 3 tumors with
an axis of 2.0+/-0.1 mm, respectively, in contrast to only a single tumor f
or the DCA-unfed casein group (nil for the DCA-unfed HMF group). The differ
ence in tumor number and size was considered significant between these DCA-
fed casein and HMF groups; that is to say, HMF feeding retarded tumor devel
opment despite the frequent occurrence of preneoplastic lesions. In additio
n, fecal bile acid excretion was much more elevated by HMF feeding than by
casein feeding. It can be assumed from these observations that the antitumo
rigenicity of HMF is due to the inhibitory effect of soybean resistant prot
eins on reabsorption as well as the mucosal contact of bile acids in the in
testine.